1. Field of the Invention
The invention relates to insonication of an animal body, and is particularly applicable to insonication of the human brain.
2. Background Information
Among the more significant causes of death or significant disability, stroke and ischemia of the brain are major factors. Stroke is commonly caused by the formation of thrombi, i.e., blood clots formed in the circulatory system of an animal body, including to the arteries, the veins, and the capillary system. When sufficiently large as to effectively occlude a vessel, they can cause heart attack or stroke, dependent on their location. When such thrombi form, it is essential to clear them in the shortest possible time, else death or at least significant damage may ensue. The time to treatment is critical for successful stroke therapy using thrombolytic agents. Only a small percentage (less than 20%) reach a hospital in time to qualify for such treatment.
Thrombolytic agents are frequently administered to break up or clear thrombi. It has been found in in-vitro and in animal studies that the action of such agents is often considerably enhanced by the application of ultrasound to the site in which a thrombus is located, concurrent with the injection of thrombolytic agents. The precise mechanism by which this occurs is still a matter of investigation but, regardless of the mechanism, the fact of improvement over a broad range of cases is well established.
The most common application of therapeutic ultrasound has been to the torso. Here, both external and catheter-delivery approaches have been used. Frequently, imaging procedures have first been used to locate a clot, and then therapeutic ultrasound is applied to reduce or eliminate the clot. The procedures are most commonly performed in hospitals, and by skilled medical personnel.
Blood clots in the brain have presented severe challenges to medical intervention. Because of the high risk associated with procedures affecting the brain, such procedures are typically left to the hands of highly skilled physicians called interventionalists. To the extent that ultrasound is used by such specialists, it is applied by way of intraarterial catheter. The procedure is difficult, time consuming, and carries significant risk, even when performed by highly skilled personnel. In a different but related disease, Vascular Cognitive Insufficiency (VCI), brain function is compromised by long term lack of blood flow. Thus, procedures which could temporarily or permanently increase blood flow to under-perfused regions of the brain would be of great value.
Similar considerations apply to treatment of ischemia. Recent studies in animal bodies have shown that ultrasound may enhance perfusion in ischemic tissue: see Siegel, J American College of Cardiology 1992; 20-732-5; Francis, Circulation 2000; 101:2296-2301. However, utilization of this approach for treatment of ischemia in the brain encounters all the obstacles faced when applying ultrasound to the brain for treatment of emboli.
Sonic therapy devices are most commonly employed in controlled environments such as hospitals, physician's offices, and the like, where size and transportability of the equipment are typically not major considerations, and where highly skilled personnel are generally available to operate the equipment. Such equipment is far less suited to environments such as ambulances and other emergency medical vehicles, where space is at a premium and where the personnel are commonly less intensively trained than those encountered in the typical hospital or private medical office setting.
Insonication of the brain presents unusual difficulties. The reasons are several. To begin with, unlike the torso, the skull is a significant barrier to the transmission of ultrasound energy through it. Thus, a large portion of the energy that is applied to the skull is consumed merely in heating the skull and raising its temperature at typical therapeutic frequencies. This limits the amount of energy that can be applied to dissolving the blood clot and can also cause patient discomfort and even injury if not carefully monitored.
Further, the precise location of an embolus of an area of inadequate perfusion within the body is frequently not known. Accordingly, it is necessary to provide the insonication over a large spatial extent. In the brain, for example, the volume to be treated may extend over a region on the order of 5 cm in diameter. Because of the uncertainty of the location of a thrombus in the region to be insonicated, it is desirable to provide a uniform intensity of insonication over the entire region, lest the specific site at which the thrombus is located receive too little energy or other sites too much. The need for coverage over an extended region, however, and that for uniform insonication over that region, present opposing considerations.
Specifically, the extent of field covered by a transducer varies inversely with the size of the transducer. Thus, a single large transducer will create a uniform field of only limited extent. Although arrays of transducers are known in other contexts (e.g., in application of ultrasound to the torso) in order to provide phased array scanning of a large area (see, for example, U.S. Pat. No. 6,384,516, issued May 7, 2002 to Fraser for “Hex Packed Ultrasonic Transducer Arrays”) such scanning sweeps over a field a portion at a time, and does not irradiate an extended region uniformly. In addition, it requires many small elements and complex drive electronics to accomplish the scanning function. Similarly, U.S. Pat. No. 5,713,831, issued Feb. 3, 1998 to Olsson for “Method and Apparatus For Arterial Reperfusion Through Noninvasive Ultrasonic Action” proposes to use an array of transducers, each independently excited, to cover a larger area than that covered by a single transducer. Again, however, the field is effectively scanned, and the radiation is non-uniform.